In this study we compared the pressor, renal and endocrine effects of the physiological precursor of endothelial derived nitric oxide, L-arginine, with D-glucose, a substrate inactive on nitric oxide. Ten subjects with mild to moderate primary hypertension underwent infusion with either L-arginine (5 patients) or D-glucose (5 patients). The substances were infused over 25 min at equiosmolar rates, preceded and followed by a 25-min saline infusion. Blood pressure (BP) and heart rate were monitored at 3-min intervals; hormonal and humoral variables, inulin and para-aminohippurate clearance, and electrolyte excretion were measured at the end of each period at maximum diuresis. L-arginine and D-glucose brought about comparable increases in serum osmolality and similar hemodilution as compared with control saline. During L-arginine infusion, systolic and diastolic BP dropped by 16.6% and 11% respectively and recovered during the post-infusion period. Heart rate, plasma renin activity, and plasma norepinephrine did not change significantly. The percent BP decrease induced by L-arginine was significantly greater than that caused by D-glucose. Glomerular filtration rate remained stable, and renal plasma flow increased with both substances. However, only L-arginine stimulated markedly natriuresis, kaliuresis, and chloruresis. It also seemed to induce systemic acidosis, possibly as a consequence of hydrochloric acid generated during its metabolism. Circulating insulin, atrial natriuretic peptide, growth hormone, and glucagon levels increased, and plasma aldosterone remained unchanged during L-arginine infusion. During D-glucose infusion, insulin was stimulated and the other hormones were inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)